Found 1 Presentation For Request "880P"
880P - Phase II trial of the cyclin dependent kinase 4/6 inhibitor SHR6390 in patients with advanced head and neck mucosal melanoma harboring CDK4 amplification
- Chaoji Shi (Shanghai, China)
Abstract
Background
Mucosal melanoma (MM) is a rare but devastating subtype of melanoma with 5-year survival rates ranging from only 16% to 25%. Our previous studies have demonstrated robust anti-tumor effects of CDK 4/6 inhibitors in head and neck MM (HNMM) patients (pts) derived xenograft models with CDK4 amplification. We performed a phase II study to determine the efficiency and safety of SHR6390, a CDK4/6 inhibitor, in pts with HNMM harboring CDK4 amplification.
Methods
In this phase II trial, advanced recurrent and/or metastatic HNMM pts with CDK4 amplification were treated with SHR6390 125 mg once daily for 21 consecutive days in 28-day cycles. The primary endpoint was disease control rate (DCR) per RECIST v1.1, which included complete response (CR), partial response (PR), stable disease (SD). Secondary endpoints included safety, objective response rate (ORR) and progression free survival (PFS).
Results
Up to Apr 2022, 17 pts who have failed ≥1 prior therapies were enrolled in this study. The median age of the pts was 56 years (ranged 29-73 years), 8 pts (47.1%) were male. All pts had ECOG PS 1, 10 pts (58.8%) had received chemotherapy treatment, and 11 pts (64.7%) had received prior PD-1 inhibitor therapy. Of 15 evaluable pts, 11 pts had SD and the best clinical response was a PR in one pt. The PR is still ongoing for more than 13 months (tumor shrinkage >80%). The ORR and DCR were 6.7% and 80.0%, respectively. With a median follow-up of 10.1 months, the estimated median PFS was 5.5 months, and the median OS was not reached. At data cutoff, 7 pts remained on treatment. Treatment-related adverse events (TRAEs) occurred in 100.0% of pts, and most TRAEs were grade 1-2. The most frequent AEs were neutrophil count decreased (64.7%), white blood cell count decreased (64.7%), and fatigue (41.2%). Only 1 pt experienced grade 3 neutrophil count decreased and white blood cell count. No grade 4/5 AEs were reported.
Conclusions
This study showed that SHR6390 was well-tolerated and appeared to be effective in HNMM pts harboring CDK4 amplification, which hints that it’s worthy to further explore SHR6390 in combination with other drugs in the systemic treatment of advanced MM.
Clinical trial identification
ChiCTR2000031608.
Editorial acknowledgement
We thank Jiangsu Hengrui Medicine Co., Ltd (Jiangsu, China) which kindly provided CDK4/6 inhibitor SHR6390.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.